Structural insights into inhibition of the drug target dihydroorotate dehydrogenase by bacterial hydroxyalkylquinolines

RSC Chem Biol. 2022 Feb 7;3(4):420-425. doi: 10.1039/d1cb00255d. eCollection 2022 Apr 6.

Abstract

Hydroxyalkylquinolines (HAQs) are ubiquitious natural products but their interactions with associated protein targets remain elusive. We report X-ray crystal structures of two HAQs in complex with dihydroorotate dehydrogenase (DHODH). Our results reveal the structural basis of DHODH inhibition by HAQs and open the door to downstream structure-activity relationship studies.